Category: Metabolism obesity and metabolic diseases


Sagar P. Bapat, MD, PhD

Research Interests:
Development of a novel T cell therapy to induce beige adipogenesis

Summary:
Type 2 diabetes is a leading cause of mortality in the United States, and its prevalence continues to rise in concert with the rising prevalence of obesity, the predominant risk factor for developing insulin resistance and diabetes. Obesity can result from a multitude of different complex physiological and socioeconomic conditions that individuals are often unable to overcome. Simply stated however, obesity is a manifestation of excessive storage of energy. Consequently, it could potentially be mitigated by turning on the body’s dormant systems for burning, not storing, that energy. In this proposal, we will develop regulatory T (Treg) cells as a powerful class of engineered, non-destructive cellular immunotherapies to tackle obesity and its co-associated metabolic disease type 2 diabetes. We will engineer fat-localizing Treg cells to deliver signals to convert energy-storing adipose tissue (AT) into energy-burning AT, thereby reversing or preventing obesity and insulin resistance in mice (and eventually humans.)

https://diabetes.ucsf.edu/lab/bapat-lab

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Biao Wang, Ph.D.

WangB

Research Interests:
Obesity, diabetes, hormones, cAMP, kinase, signaling transduction, transcriptional regulation

Summary:
Type II diabetes mellitus accounts for 90-95% of all cases of diabetes, and this heterogeneous disorder afflicts an estimated 6% of the adult population in Western society. Energy imbalance by high calorie intake and/or lack of physical activity can lead to obesity, which is often associated with an increased risk of developing insulin resistance followed by type II diabetes. Our research is focused on understanding how circulating hormones modulate energy balance in multiple metabolic tissues, and how disruption of these hormonal actions contributes to pathophysiology of type II diabetes.

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Takashi Mikawa, M.S., Ph.D.

Mikawa

Research Interests:
Morphogenesis, development, body axis, patterning, cell-to-cell communication, cell architecture, cell fate diversification, cardiovascular system, cardiac conduction system, central nervous system, haemodynamics, growth factor signaling.

Summary:
The establishment of extremely complicated structures and functions of our organ systems depends upon orchestrated differentiation and integration of multiple cell types. Our group focuses to explore a common developmental plan for successful organogenesis, by investigating the mechanisms involved in the differentiation and patterning of the cardiovascular and central nervous systems.

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Dengke Ma, Ph.D.

Ma

Research Interests:

Genetic approaches to understanding physiology and diseases, oxygen-modulated metabolism and behavior; brain-heart-lung interaction and interoception; ischemic disease and tolerance; novel genes and pathways evolutionarily conserved in C. elegans and humans.

Summary:
As humans, we drink when thirsty, eat when hungry, and increase our breathing and heart rates when short of oxygen. How do we (our bodies) know when and how to respond to changes in internal bodily states (e.g. loss of nutrient or oxygen)? Genes and traits that facilitate such underlying mechanisms confer great advantages for animal survival and are strongly selected for during evolution. Using both C. elegans and tractable mammalian model systems, we seek to understand the molecular, cellular and neural circuit basis of how animals sense and respond to changes in internal metabolic and energetic states to elicit behavior and maintain homeostasis. Dysfunction of these fundamental physiological processes leads to many disorders, including obesity, diabetes, neurological and cardiovascular diseases.

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Ronald M Krauss, M.D.

Krauss

Research Interests:
Summary:
Lipoprotein metabolism and risk of cardiovascular disease

Despite recent advances in treatment, cardiovascular disease (CVD) remains the leading cause of death in the US and will soon achieve this status globally. Our group’s research is aimed at addressing three major challenges for reducing this enormous disease burden. First, standard diagnostic procedures do not identify a high proportion of children and adults who are at risk for CVD. We have developed and implemented a sophisticated new procedure that, by analyzing individual lipoprotein particles, provides more specific information than that afforded by ordinary cholesterol testing, and hence is capable of improving both the assessment and management of CVD risk. Second, dietary and lifestyle guidance has failed to substantially impact CVD risk factors, particularly those related to overweight and obesity. We have demonstrated that carbohydrate restriction can reverse the high risk lipid profile found in a high proportion of overweight and obese individuals even without weight loss, and that this effect is independent of saturated fat intake. These findings have helped support dietary guidelines that place a greater emphasis on limiting refined carbohydrates than fats. Third, despite the awareness of wide interindividual variability in response to treatments aimed at reducing CVD risk, the potential benefits of applying genomic tools for developing personalized approaches for maximizing CVD risk reduction have not been realized. A major component of our research program has been the application and development of genomic methodology for dissecting genetic influences on the therapeutic responses to statins, the most widely prescribed class of drugs for reducing CVD risk.

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John P Kane, M.S., M.D., Ph.D.

Kane

Research Interests:
Structure and function of lipoproteins; genetic determinants of arteriosclerosis

Summary:
The Kane laboratory focuses on the discovery of the native structures of lipoproteins ( proteins that carry cholesterol so that we can better understand how they are involved in the development of heart disease and stroke. We are also active in the discovery of alterations in genes that lead to heart disease and stroke.

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Allison Wanting Xu, M.Sc., Ph.D.

Xu

Research Interests:
Hypothalamic regulation of energy balance, obesity and type 2 diabetes

Summary:
Our lab’s major research focus is to understand the mechanisms by which energy balance is regulated. We use a combination of mouse genetics, whole body physiology and real time imaging approaches to elucidate the function of specific hypothalamic neurons and how they integrate peripheral metabolic signals under distinct physiologic conditions.

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Kaveh Ashrafi, Ph.D.

Ashrafi

Research Interests:
Genetics of fat regulation and neurobiology of feeding behavior

Summary:
Obesity is a major risk factor associated with many diseases including diabetes, cardiovascular and gastrointestinal diseases, arthritis, and certain forms of cancers. The prevalence of obesity reflects the combination of high calorie diets with sedentary lifestyles. However, genetic predispositions play profound roles in determination of an individual’s fat. How genetic and environmental factor interact to determine fat content and how excess fat accumulation causes disease processes are poorly understood. To identify genes that underlie fat regulation we use the genetically tractable worm C. elegans. This system has allowed us to discover novel fat regulatory pathways, compounds that alter fat content, and probe the neural circuits that regulate fat and feeding.

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